Entry |
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Name |
Amyotrophic lateral sclerosis (ALS); Lou Gehrig disease |
Description |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive degeneration of motor neurons in the brain and spinal cord. In 90% of patients, ALS is sporadic, with no clear genetic linkage. On the other hand, the remaining 10% of cases show familial inheritance, with mutations in SOD1, TDP43(TARDBP), FUS, or C9orf72 genes being the most frequent causes. In spite of such difference, familial ALS and sporadic ALS have similarities in their pathological features. Proposed disease mechanisms contributing to motor neuron degeneration in ALS are: impaired proteostasis, aberrant RNA processing, mitochondrial disfunction and oxidative stress, microglia activation, and axonal dysfunction.
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Category |
Neurodegenerative disease
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Brite |
Human diseases [BR:br08402]
Nervous system diseases
Neurodegenerative diseases
H00058 Amyotrophic lateral sclerosis (ALS)
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Motor neuron diseases or related disorders
8B60 Motor neuron disease
H00058 Amyotrophic lateral sclerosis (ALS)
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Pathway |
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Network |
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Element |
N01135 | Mutation-caused aberrant SOD1 to intrinsic apoptotic pathway |
N01136 | Mutation-caused aberrant TDP43 to electron transfer in Complex I |
N01138 | Mutation-inactivated OPTN to PINK-Parkin-mediated autophagosome formation |
N01139 | Mutation-inactivated p62 to PINK-Parkin-mediated autophagosome formation |
N01141 | Mutation-inactivated TBK1 to TBK1-mediated autophagosome formation |
N01143 | Mutation-inactivated C9orf72 to C9orf72-mediated autophagy initiation |
N01144 | Mutation-caused aberrant SOD1 to 26S proteasome-mediated protein degradation |
N01145 | Mutation-inactivated VCP to 26S proteasome-mediated protein degradation |
N01146 | Mutation-inactivated UBQLN2 to 26S proteasome-mediated protein degradation |
N01147 | Mutation-caused aberrant SOD1 to ATF6-mediated transcription |
N01148 | Mutation-caused aberrant SOD1 to IRE1a-XBP1 signaling pathway |
N01149 | Mutation-caused aberrant SOD1 to PERK-ATF4 signaling pathway |
N01150 | Mutation-inactivated VAPB to ATF6-mediated transcription |
N01151 | Mutation-inactivated SIGMAR1 to Ca2+ -apoptotic pathway |
N01153 | Mutation-caused aberrant GLE1 to nuclear export of mRNA |
N01155 | Mutation-caused aberrant TDP43 to TDP-43-regulated splicing |
N01157 | Mutation-caused aberrant FUS to FUS-regulated splicing |
N01158 | Mutation-caused aberrant DCTN1 to retrograde axonal transport |
N01159 | Mutation-caused aberrant TUBA4A to retrograde axonal transport |
N01160 | Mutation-caused aberrant SOD1 to retrograde axonal transport |
N01162 | Mutation-caused aberrant PFN1 to actin polymerization |
N01164 | Mutation-inactivated ERBB4 to NRG-ERBB4-PI3K signaling pathway |
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Gene |
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Drug |
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Comment |
Affected region: motor cortex, brain stem, spinal cord
Microscopic lesion: hyaline inclusions
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Other DBs |
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Reference |
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Authors |
Mathis S, Goizet C, Soulages A, Vallat JM, Masson GL |
Title |
Genetics of amyotrophic lateral sclerosis: A review. |
Journal |
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Reference |
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Authors |
Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH |
Title |
Amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE |
Title |
Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. |
Journal |
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Reference |
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Authors |
Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH Jr |
Title |
Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Chow CY, Landers JE, Bergren SK, Sapp PC, Grant AE, Jones JM, Everett L, Lenk GM, McKenna-Yasek DM, Weisman LS, Figlewicz D, Brown RH, Meisler MH |
Title |
Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. |
Journal |
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Reference |
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Authors |
Turner MR, Kiernan MC, Leigh PN, Talbot K |
Title |
Biomarkers in amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Rutherford NJ, Zhang YJ, Baker M, Gass JM, Finch NA, Xu YF, Stewart H, Kelley BJ, Kuntz K, Crook RJ, Sreedharan J, Vance C, Sorenson E, Lippa C, Bigio EH, Geschwind DH, Knopman DS, Mitsumoto H, Petersen RC, Cashman NR, Hutton M, Shaw CE, Boylan KB, Boeve B, Graff-Radford NR, Wszolek ZK, Caselli RJ, Dickson DW, Mackenzie IR, Petrucelli L, Rademakers R |
Title |
Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Pasinelli P, Brown RH |
Title |
Molecular biology of amyotrophic lateral sclerosis: insights from genetics. |
Journal |
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Reference |
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Authors |
Gros-Louis F, Gaspar C, Rouleau GA |
Title |
Genetics of familial and sporadic amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH Jr, Hardiman O |
Title |
ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Valentine JS, Doucette PA, Zittin Potter S |
Title |
Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Kunst CB |
Title |
Complex genetics of amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Chen YZ, Bennett CL, Huynh HM, Blair IP, Puls I, Irobi J, Dierick I, Abel A, Kennerson ML, Rabin BA, Nicholson GA, Auer-Grumbach M, Wagner K, De Jonghe P, Griffin JW, Fischbeck KH, Timmerman V, Cornblath DR, Chance PF |
Title |
DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). |
Journal |
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Reference |
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Authors |
Julien JP. |
Title |
Amyotrophic lateral sclerosis. unfolding the toxicity of the misfolded. |
Journal |
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Reference |
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Authors |
Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada M, Nodera H, Suzuki H, Komure O, Matsuura S, Kobatake K, Morimoto N, Abe K, Suzuki N, Aoki M, Kawata A, Hirai T, Kato T, Ogasawara K, Hirano A, Takumi T, Kusaka H, Hagiwara K, Kaji R, Kawakami H |
Title |
Mutations of optineurin in amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Yamashita S, Ando Y |
Title |
Genotype-phenotype relationship in hereditary amyotrophic lateral sclerosis. |
Journal |
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Reference |
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Authors |
Sieh W, Choi Y, Chapman NH, Craig UK, Steinbart EJ, Rothstein JH, Oyanagi K, Garruto RM, Bird TD, Galasko DR, Schellenberg GD, Wijsman EM |
Title |
Identification of novel susceptibility loci for Guam neurodegenerative disease: challenges of genome scans in genetic isolates. |
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